Molecular characterization and expression analysis of mouse epidermal growth factor-like domain 8

Song, Ik-Jin; Ikram, Muhammad; Subhan, Fazli; Choi, Da-Jeong; Lee, Ja-Rang; Kim, Heui-Soo; Lim, Yooseong; Yoon, Sik

doi:10.3892/ijmm.2015.2252

Cited by 5 publications

(9 citation statements)

References 36 publications

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“…Epidermal growth factor‐like domain multiple 6 (EGFL6) is an extracellular matrix protein, belongs to EGFL family and plays an important role in promoting the migration and angiogenesis of endothelial cells . Recently, it is reported that EGFL6 regulates the metastasis of ALDH + ovarian cancer cells and is overexpression in benign meningioma and oral squamous cell carcinoma . Moreover, EGFL6 implicates in the pathogenesis of benign meningioma via activating AKT pathway .…”

Section: Introductionmentioning

confidence: 99%

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Zhu

You

et al. 2018

Cancer Medicine

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Epidermal growth factor‐like domain multiple 6 (EGFL6) is a secreted protein, regulates maintenance and metastasis of cancer cells. Nevertheless, how EGFL6 participates in the progression and tumorigenesis of nasopharyngeal carcinoma (NPC) remains unclear. In our study, EGFL6 was detected highly expressed in 20 NPC tissues compared with normal tissues by IHC assay. Then, the level of EGFL6 in NPC serum and NPC cells was explored through enzyme‐linked immunosorbent assay and western blot, the results consistent with IHC. More interestingly, EGFL6 accelerated the migration and growth of NPC in vitro assays. Considering the mechanism of migration, NPC cells were cultured with AKT activator, revealing EGFL6 facilitated the progression of NPC via AKT. Moreover, the same effect of EGFL6 in promoting NPC growth was proved in nude mice. Furthermore, heat‐shock zebrafish model was established with EGFL6 overexpression. Then, CNE2 cells were injected into the model and cells mass was observed, showing that EGFL6 enhanced the migration and metastasis of NPC. Currently, as the prognosis of NPC is severely affected by distant metastasis, it might be a new therapeutic target toward EGFL6. Taken together, our results suggested that EGFL6 acts as a potential positive regulator in the migration and proliferation of NPC.

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Section: Introductionmentioning

confidence: 99%

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Zhu

You

et al. 2018

Cancer Medicine

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“…Significant differences were observed in the expression of EGFL gene family among different types of tumors, as well as among different members of EGFL family within each tumor type, demonstrating the need to study each gene member as a separate entity. In tumorigenesis, one typical functional feature of these genes was their expression dysregulation in tumors, and increasingly, evidence supported the conclusion that the expression of the EGFL family members changes in different tumors (Wu et al, 2011a;Nichol and Stuhlmann, 2012;Song et al, 2015). However, the majority of the evidence has been provided by the studies on cell lines or animal models.…”

Section: Egfl Domains Gene Expression In Pan-cancermentioning

confidence: 96%

“…EGFL6, 7, and 8 have been partially studied in CRC (Song et al, 2015;Hong et al, 2018;Zhang et al, 2019). In this study, TCGA CRC data were used to conduct a comprehensive study of EGFL genes in one of the largest CRC patient cohort publicly available.…”

Section: Egfl Domain Gene Family In Colorectal Cancermentioning

confidence: 99%

“…They not only have a similar structure and functional characteristics but also have a unique structure and function. They play a certain potential role in tumor occurrence, development, and prognosis because their expression is different in various tumors, indicating that they can provide new options for tumor treatment (Song et al, 2015;Kang et al, 2020). On the basis of investigations and experiments, we discussed the relationship among EGFL6, −7, and −8 and tumor development and prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…However, compared with normal tissues, the expression level of EGFL8 is significantly reduced in colorectal cancer (CRC) tissues (Wu et al, 2011b) and gastric cancer tissues (Wu et al, 2011a). Moreover, a link has been established between the downregulation of EGFL8 and CRC (Wu et al, 2011b) and GC (Song et al, 2015) metastasis and poor prognosis. In conclusion, EGFL6, 7, and 8 are more likely to offer a breakthrough for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

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A Pan-Cancer Study of Epidermal Growth Factor-Like Domains 6/7/8 as Therapeutic Targets in Cancer

Shi

2020

Front. Genet.

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With highly homologous epidermal growth factor (EGF)-like (EGFL) domains, the members of the EGFL family play crucial roles in growth, invasion, and metastasis of tumors and are closely associated with the apoptosis of tumor cells and tumor angiogenesis. Furthermore, their contribution to immunoreaction and tumor microenvironment is highly known. In this study, a comprehensive analysis of EGFL6, −7, and −8 was performed on the basis of their expression profiles and their relationship with the rate of patient survival. Through a pan-cancer study, their effects were correlated with immune subtypes, tumor microenvironment, and drug resistance. Using The Cancer Genome Atlas pan-cancer data, expression profiles of EGFL6, −7, and −8, and their association with the patient survival rate and tumor microenvironment were analyzed in 33 types of cancers. The expression of the EGFL family was different in different cancer types, revealing the heterogeneity among cancers. The results showed that the expression of EGFL8 was lower than EGFL6 and EGFL7 among all cancer types, wherein EGFL7 had the highest expression. The univariate Cox proportional hazard regression model showed that EGFL6 and EGFL7 were the risk factors to predict poor prognosis of cancers. Survival analysis was then used to verify the relationship between gene expression and patient survival. Furthermore, EGFL6, EGFL7, and EGFL8 genes revealed a clear association with immune infiltrate subtypes; they were also related to the infiltration level of stromal cells and immune cells with different degrees. Moreover, they were negatively correlated with the characteristics of cancer stem cells measured by DNAs and RNAs. In addition, EGFL6, −7, and −8 were more likely to contribute to the resistance of cancer cells. Our systematic analysis of EGFL gene expression and their correlation with immune infiltration, tumor microenvironment, and prognosis of cancer patients emphasized the necessity of studying each EGFL member as a separate entity within each particular type of cancer. Simultaneously, EGFL6, −7, and −8 signals were verified as promising targets for cancer therapies, although further laboratory validation is still required.

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Functional EGF domain of the human neuregulin 1α produced in Escherichia coli with accurate disulfide bonds

et al. 2022

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Background Neuregulins comprise a large family of growth factors containing an epidermal growth factor (EGF) domain. NRG1 acts in signaling pathways involved in proliferation, apoptosis, migration, differentiation, and adhesion of many normal cell types and in human diseases. The EGF domain of NRG1 mediates signaling by interaction with members of the ErbB family of receptors. Easy access to correctly folded hNRG1α EGF domain can be a valuable tool to investigate its function in different cell types. Materials and methodsThe EGF domain of hNRG1α was produced in Escherichia coli in fusion with TrxA and purified after cleavage of TrxA. Conformation and stability analyses were performed by using biophysical methods and the disulfide bonds were mapped by mass spectrometry. The activity of the hNRG1α EGF domain was demonstrated in cell proliferation and migration assays. Results Approximately 3.3 mg of hNRG1α EGF domain were obtained starting from a 0.5 L of E. coli culture. Correct formation of the three disulfide bonds was demonstrated by mass spectrometry with high accuracy. Heat denaturation assays monitored by circular dichroism and dynamic light scattering revealed that it is a highly stable protein. The recombinant EGF domain of hNRG1α purified in this work is highly active, inducing cell proliferation at concentration as low as 0.05 ng/mL. It induces also cell migration as demonstrated by a gap closure assay. ConclusionThe EGF domain of hNRG1α was produced in E. coli with the correct disulfide bonds and presented high stimulation of HeLa cell proliferation and NDFH cell migration. KeywordsHuman Neuregulin-1 • Recombinant EGF domain • Disulfide bond assignment • hNRG1α EGF domain activity * Nilson I. T. Zanchin

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Molecular characterization and expression analysis of mouse epidermal growth factor-like domain 8

Cited by 5 publications

References 36 publications

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma

A Pan-Cancer Study of Epidermal Growth Factor-Like Domains 6/7/8 as Therapeutic Targets in Cancer

Functional EGF domain of the human neuregulin 1α produced in Escherichia coli with accurate disulfide bonds

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